Angiotensin-Converting Enzyme Inhibitor Use and Incident Frailty: A Longitudinal Cohort Study

Abstract

Introduction: Angiotensin-converting-enzyme inhibitors (ACEI) may have several pleiotropic effects, but the literature regarding a possible relationship between ACEI use and frailty is limited.We investigated whether ACEI use is associated with lower risk of frailty in a cohort of North American individuals.Methods: Data from the Osteoarthritis Initiative, a cohort study with 8 years of follow-up including community-dwelling adults with knee osteoarthritis or at high risk for this condition, were analyzed. ACEI use was defined through self-reported information and confirmed by a trained interviewer.Frailty was defined using the Study of Osteoporotic Fracture (SOF) index as the presence of at least two of the following criteria: (i) weight loss ≥5% between baseline and any subsequent follow-up visit; (ii) inability to do five chair stands; and (iii) low energy level according to the SOF definition.A multivariable Poisson regression analysis was used to assess the association between ACEI use at baseline and incident frailty. The data were reported as relative risks (RRs) with their 95% confidence intervals (CIs). Results:The final sample consisted of 4,295 adults (mean age 61.2 years, females=58.1%). At baseline, 551 participants (12.8%) used ACEI. After adjusting for 15 potential confounders, the use of ACEI was associated with a lower risk of frailty (RR=0.72; 95%CI: 0.53-0.99). The adjustment for the propensity score substantially confirmed these findings (RR=0.75; 95%CI: 0.54-0.996). Conclusion:ACEI use may be associated with a reduced risk of frailty in individuals with/at risk of knee osteoarthritis, suggesting a potential role for ACI in the prevention of frailty.

Mini-review: Angiotensin- converting enzyme 1 (ACE1) and the impact for diseases such as Alzheimer’s disease, sarcopenia, cancer, and COVID-19

“… Witham et al (2014) followed 639 individuals (mean age 65 years) during 4.4 years and observed no difference in grip strength change per year in ACEi users. However, in patients with knee osteoarthritis, a study of 8 years follow-up of 4,295 individuals (mean age 61.2 years) showed that ACEi use (12.8% of participants) was correlated with a reduced risk of frailty ( Veronese et al, 2019 ). Preliminary findings have also indicated beneficial effects of other RAS inhibitors such as ARBs and renin inhibitors, mostly because of their inhibitory effects on local inflammation and oxidative stress.…”

A comprehensive health education plus monitoring support program for older adults with knee osteoarthritis coexisting with overweight and type 2 diabetes

“…According to the prevalence and coexistence of KOA, a common coexisting condition is type 2 diabetes mellitus (T2DM), making KOA more difficult to manage [ [1] , [2] , [3] ]. T2DM not only shares risk factors with osteoarthritis [ 4 , 5 ], but also its pathological pathways influence inflammation processes and increase adverse outcomes [ 6 ]. Moreover, being overweight or obese is prevalent in older adults with KOA and T2DM, and it aggravates the risks of developing KOA symptoms and intensifying severity [ 4 , 5 ].…”

“…KOA mostly occurs with coexisting morbidity, particularly T2DM. For T2DM, recent evidence revealed that pathological pathways—chronic hyperglycemia and insulin resistance—significantly influence the inflammation processes and increase adverse outcomes in the osteoarthritis population [ 6 ]. Additionally, T2DM shares risk factors with osteoarthritis [ 4 , 5 ]; the prevalence of older people diagnosed with both KOA and T2DM continues to increase [ [1] , [2] , [3] ].…”

“…Hence, a person with KOA who experienced T2DM with increasing body weight is more likely to increase the risk of severe arthritis and altered joint loading resulting in a poor prognosis of KOA. Suffering from KOA severity, chronic pain, and poor outcomes are not only associated with, but also shared influenced by both T2DM and being overweight or obese [ [4] , [5] , [6] ]. Coexisting conditions of T2DM and obesity or being overweight is predominant in older adults with KOA leading to increased risk of dependency, long-term care needs, and poor QOL.…”